Neural crest cells migrate extensively and precisely in the developing vertebrate embryo. These cells ultimately contribute to part or all of such diverse structures as: pigment cells, sensory and autonomic ganglia, the cranial cartilages and teeth. There is considerable experimental evidence that cells are pluripotent when they migrate, and that the pattern of migration and differentiation is controlled by environmental factors. In mice there are a number of mutants affecting neural crest development. They result in different patterns of pigmentation and various other developmental abnormalities in crest derivatives ranging from severe cranio-facial lesions, to reduced numbers and/or altered distribution of sensory and autonomic neurons. Some of these mutants are embryonic lethals as homozygotes. Using a variety of histological and histochemical procedures, at the light and EM levels, we propose to test the hypothesis that some of these developmental abnormalities result from changes in the temporal and spatial patterns of synthesis, deposition and removal of glycosaminoglycans comprising the extracellular matrix. We further propose to analyse how such extracellular matrix materials affect the morphogenetic behavior and differentiation of neural crest cells in vitro.